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Biomedical subjects

E S Hughes

Publications and source records attributed to E S Hughes.

At least 19 recordsLinked to original sources

In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop.

The distribution, cell tropism, and cytopathology in vivo of human immunodeficiency virus (HIV) was investigated in postmortem tissue samples from a series of HIV-infected individuals who died either of complications associated with AIDS or for unrelated reasons while they were asymptomatic. Proviral sequences were detected at a high copy number in lymphoid tissue of both presymptomatic patients and patients with AIDS, whereas significant infection of nonlymphoid tissue such as that from brains, spinal cords, and lungs were confined to those with AIDS. V3 loop sequences from both groups showed highly restricted sequence variability and a low overall positive charge of the encoded amino acid sequence compared with those of standard laboratory isolates of HIV type 1 (HIV-1). The low charge and the restriction in sequence variability were comparable to those observed with isolates showing a non-syncytium-inducing (NSI) and macrophage-tropic phenotype in vitro. All patients were either exclusively infected (six of seven cases) or predominantly infected (one case) with variants with a predicted NSI/macrophage-tropic phenotype, irrespective of the degree of disease progression. p24 antigen was detected by immunocytochemical staining of paraffin-fixed sections in the germinal centers within lymphoid tissue, although little or no antigen was found in areas of lymph node or spleen containing T lymphocytes from either presymptomatic patients or patients with AIDS. The predominant p24 antigen-expressing cells in the lungs and brains of the patients with AIDS were macrophages and microglia (in brains), frequently forming multinucleated giant cells (syncytia) even though the V3 loop sequences of these variants resembled those of NSI isolates in vitro. These studies indicate that lack of syncytium-forming ability in established T-cell lines does not necessarily predict syncytium-forming ability in primary target cells in vivo. Furthermore, variants of HIV with V3 sequences characteristic of NSI/macrophage-tropic isolates form the predominant population in a range of lymphoid and nonlymphoid tissues in vivo, even in patients with AIDS.

Acquired Immunodeficiency Syndrome

Obstructing carcinomas of the colon.

A series of 908 cases of colonic carcinoma has been analysed to elucidate reasons for the poor prognosis in obstructing colonic cancer. Complete obstruction was present in 148 cases (16.3 per cent), 280 cases (30.8 per cent) had partial obstruction and 480 (52.8 per cent) presented without obstruction. There were fewer Dukes' A tumours in those with complete obstruction (P less than 0.005) and greater numbers of advanced tumours (P less than 0.0005) compared with those without obstruction. This is reflected in a lower curative resection rate of 50.7 per cent in those with obstruction compared with 70.6 per cent in those without obstruction (P less than 0.001). However, after curative resection there was no significant difference in the distribution of tumour stage. Patients with complete obstruction showed a higher incidence of recurrence (P less than 0.01) after curative resection, consequent to an increased incidence of local recurrence (P less than 0.02). Five-year cancer-specific survival for the total series was decreased from 59.1 per cent in patients without obstruction to 31.8 per cent in those with complete obstruction (P less than 0.001). After curative resection there was also a significant reduction in survival (P less than 0.001). It is concluded that completely obstructing colonic cancers are more aggressive than other colonic cancers.

Adult

Lung recurrence after curative surgery for colorectal cancer.

A total of 1578 patients were treated with potentially curative surgical resection for colon and rectal cancer by one surgeon from 1950 to 1982. Follow-up revealed that 117 (11.5 percent) of 1013 patients with rectal carcinoma eventually presented with clinical evidence of pulmonary recurrence, with or without evidence of spread elsewhere; the corresponding figures for the colon were 20 (3.5 percent) of 565 (P less than 0.001). An analysis of the times to recurrence revealed that half of the lung recurrences were clinically obvious within 32 months for rectal tumors and 34 months for colonic, compared to 22 and 21 months, respectively, for liver recurrences, excluding those with other distant metastases. The slower recurrence rate and the longer survival in patients with recurrences in the lung compared to the liver were statistically significant only for rectal primaries (P less than 0.02 and P = 0.001, respectively). Sixteen patients underwent surgery with curative intention for lung recurrences; four of these remain alive at two, six, 11, and 15 years, and one patient was free of recurrence when he died from other causes 15 months after surgery. The conditional probability survival rate for the 16 patients was 38 +/- 13 percent at five years after recurrence operation.

Colonic Neoplasms

Aggressive angiomyxoma of the female pelvis.

A 42 year old female presented with a 6 year history of a perineal mass. Clinically it had all the features of a perineal hernia. Two previous attempts to repair the 'hernia' had been performed. At operation an aggressive angiomyxoma of the female pelvis was identified and resected via an abdomino-perineal combined approach. The case is discussed with reference to the literature.

Adult

Changing survival prospects in rectal carcinoma. A series of 1,306 patients managed by one surgeon.

Cancer-specific survival prospects for rectal carcinoma in a series of 1306 patients managed from 1950 to 1979 by one surgeon worsened from 1970 to 1979. The prognosis was worse for all patients treated operatively from 1970 to 1979 compared with 1960 to 1969 (P less than 0.03). After potentially curative resection, survival was worse from 1970 to 1979 compared with 1950 to 1959 (P less than 0.02) and 1960 to 1969 (P less than 0.01), respectively; the corresponding five-year survivals were 72.5 percent, 72.3 percent, and 61.5 percent. The curative resection rate for the three decades was similar (66 to 70 percent). An increase in the incidence of Dukes' Stage C tumors from 23.3 percent to 32.3 percent (P less than 0.01) explains, at least partly, the decreased survival. The worsened survival prospects were not accounted for by changes in referral pattern, tumor site, or in the proportion of sphincter-saving resections performed. The worsening was paradoxically paralleled by earlier symptomatic presentation (P less than 0.001). Analyses of other Australian data are required to test the hypothesis that the worsened survival prospects are consequent to altered tumor biologic aggressiveness, possibly related to differences in the causal factors operating over the 30-year study period.

Adult

The outcome of patients with ulcerative colitis managed by subtotal colectomy.

A total of 1,494 patients with a diagnosis of ulcerative colitis were managed by one surgeon between 1950 and 1981. Subtotal colectomy was performed upon 286 patients of whom 82 had a primary and 65 a secondary ileorectal anastomosis. There was no significant difference in the postoperative mortalities between patients treated by subtotal colectomy (8.7 per cent) and a group of 71 patients treated by proctocolectomy (9.9 per cent). The postoperative mortality after primary and secondary ileorectal anastomosis was 6.9 and 1.5 per cent, respectively. Rectal excision because of disease activity was required in 109 patients after subtotal colectomy (13 after primary and nine after secondary ileorectal anastomosis) with a postoperative mortality of 0.5 per cent. The probability of rectal excision was 21 per cent at 12.6 years after primary anastomosis and 19 per cent at 16.2 years after secondary ileorectal anastomosis. Carcinoma of the rectum has developed in 11 (3.8 per cent) of the patients after subtotal colectomy. The probability of having carcinoma of the rectum develop was 17.1 per cent at 27 years after primary anastomosis and 20.0 per cent at 24 years after secondary ileorectal anastomoiss, the time beyond which no disease has yet been diagnosed in either group. The disease was advanced in stage and of high histologic grade with a median cancer specific survival time of 14 months.

Adult

Local recurrence after potentially curative resection for rectal cancer in a series of 1008 patients.

Local recurrence and its related mortality after potentially curative resection for rectal cancer have been analysed in a series of 1008 patients managed by one of the authors. Nine hundred and thirty-four were available for analysis of recurrence. One hundred and seven (11 per cent) patients developed local recurrence without evidence of systemic spread and 84 (9 per cent) both local and systemic recurrence. Local recurrence was less common (14 per cent) after resection of tumours of the upper third of the rectum compared with the middle (21 per cent) (P = 0.02) or lower thirds (26 per cent) (P less than 0.001). Local recurrence was related to both tumour stage and differentiation (P less than 0.001). There was no significant relationship between local recurrence and tumour size or the type of curative resection performed, restorative or non-restorative. The distal margin of clearance after restorative resection did not influence the local recurrence rate. Of patients who developed metastases recurrence was evident within 2 years in 60 per cent. Three hundred and thirty-two patients died from recurrence, 91 (27 per cent) with evidence of local recurrence only, 80 (24 per cent) with combined local and systemic recurrence and 161 (48 per cent) with evidence of systemic spread only. The corresponding median survivals were 35, 34 and 39 months.

Aged

T-antigen expression by peanut agglutinin staining relates to mucosal dysplasia in ulcerative colitis.

Staining of 326 rectal mucosal biopsies from ulcerative colitis patients with peanut agglutinin (PNA), which binds to the T-blood group antigen and has been claimed to reflect a cancer-associated mucin alteration, showed highly significant direct associations with mucosal dysplasia (P less than 0.001), disease activity (P less than 0.001), and subsequent development of rectal cancer in a smaller series of patients (P = 0.005). Staining for normal colonic mucin by the Dolichos biflorus (DBA) lectin related significantly and inversely to dysplasia. Intense normal colon mucin staining by DBA related significantly (P less than 0.025) to long disease duration and to subsequent development of cancer (P = 0.02). The latter association is based on a small number of patients only and is not considered conclusive evidence, but may provide a link with goblet-cell hyperplasia. The authors conclude that although T-antigen expression relates to dysplasia, the findings of "false" positive and negative rates of 22 and 33 percent respectively, make it unlikely that staining of biopsy sections for the T-antigen by peanut agglutinin will contribute materially to routine assessment for dysplasia and cancer risk prediction in patients with ulcerative colitis.

Adult

Total and subtotal colectomy for colonic obstruction.

Colectomy (total or subtotal) is not the operation of choice for elective colonic cancer unless the patient is under 50 years of age, is undergoing curative resection, and has associated adenomatous polyps. Routine colectomy is not supported when a partial obstruction prevents preparation of the colon and interferes with proximal colonic examination. Colectomy (especially subtotal) is acceptable for the acutely obstructed colon but it is technically demanding and requires experience in patient selection.

Adult

Prognostic significance of the absolute lymphocyte count in acute pancreatitis.

The absolute lymphocyte count was calculated with 48 hours of admission in 154 patients with acute pancreatitis. Twenty-three patients had severe pancreatitis and 131 patients had mild pancreatitis. The mean absolute lymphocyte count for the severe group was 880 +/- 102 cells/mm3 and for the mild group, 1,115 +/- 116 cells/mm3. The absolute lymphocyte count accurately predicted 78 percent of the severe attacks and 86 percent of the mild attacks.

Acute Disease

Post-proctectomy perineal hernia: case report and discussion.

Perineal hernia is a rare complication of pelvic surgery. Women are more commonly affected, and development of the condition is usually gradual. Although the true incidence of this problem is unknown, few cases are severe enough to require operative repair. We report the experience of one of the authors (E.S.R.H.) in post-proctectomy perineal hernia. One case required surgical repair and is presented, with a discussion of the operative management.

Abdomen

Gastric cancer and survival.

The survival of patients with cancer of the stomach in a Melbourne series showed no improvement over a 20-year period. Of 246 patients, 8.1% survived for a period of five years, and 4.8% survived for 10 years after presentation. A further plea is made to establish a "100%" register of cancer.

Australia